Mg2+ Effect on Argonaute and RNA Duplex by Molecular Dynamics and Bioinformatics Implications

RNA interference (RNAi), mediated by small non-coding RNAs (e.g., miRNAs, siRNAs), influences diverse cellular functions. Highly complementary miRNA-target RNA (or siRNA-target RNA) duplexes are recognized by an Argonaute family protein (Ago2), and recent observations indicate that the concentration of Mg2+ ions influences miRNA targeting of specific mRNAs, thereby modulating miRNA-mRNA networks. In the present report, we studied the thermodynamic effects of differential [Mg2+] on slicing (RNA silencing cycle) through molecular dynamics simulation analysis, and its subsequent statistical analysis. Those analyses revealed different structural conformations of the RNA duplex in Ago2, depending on Mg2+ concentration. We also demonstrate that cation effects on Ago2 structural flexibility are critical to its catalytic/functional activity, with low [Mg2+] favoring greater Ago2 flexibility (e.g., greater entropy) and less miRNA/mRNA duplex stability, thus favoring slicing. The latter finding was supported by a negative correlation between expression of an Mg2+ influx channel, TRPM7, and one miRNA’s (miR-378) ability to downregulate its mRNA target, TMEM245. These results imply that thermodynamics could be applied to siRNA-based therapeutic strategies, using highly complementary binding targets, because Ago2 is also involved in RNAi slicing by exogenous siRNAs. However, the efficacy of a siRNA-based approach will differ, to some extent, based on the Mg2+ concentration even within the same disease type; therefore, different siRNA-based approaches might be considered for patient-to-patient needs

Privacy-Preserving Federated Model Predicting Bipolar Transition in Patients With Depression:Prediction Model Development Study

BACKGROUND: Mood disorder has emerged as a serious concern for public health; in particular, bipolar disorder has a less favorable prognosis than depression. Although prompt recognition of depression conversion to bipolar disorder is needed, early prediction is challenging due to overlapping symptoms. Recently, there have been attempts to develop a prediction model by using federated learning. Federated learning in medical fields is a method for training multi-institutional machine learning models without patient-level data sharing. OBJECTIVE: This study aims to develop and validate a federated, differentially private multi-institutional bipolar transition prediction model. METHODS: This retrospective study enrolled patients diagnosed with the first depressive episode at 5 tertiary hospitals in South Korea. We developed models for predicting bipolar transition by using data from 17,631 patients in 4 institutions. Further, we used data from 4541 patients for external validation from 1 institution. We created standardized pipelines to extract large-scale clinical features from the 4 institutions without any code modification. Moreover, we performed feature selection in a federated environment for computational efficiency and applied differential privacy to gradient updates. Finally, we compared the federated and the 4 local models developed with each hospital's data on internal and external validation data sets. RESULTS: In the internal data set, 279 out of 17,631 patients showed bipolar disorder transition. In the external data set, 39 out of 4541 patients showed bipolar disorder transition. The average performance of the federated model in the internal test (area under the curve [AUC] 0.726) and external validation (AUC 0.719) data sets was higher than that of the other locally developed models (AUC 0.642-0.707 and AUC 0.642-0.699, respectively). In the federated model, classifications were driven by several predictors such as the Charlson index (low scores were associated with bipolar transition, which may be due to younger age), severe depression, anxiolytics, young age, and visiting months (the bipolar transition was associated with seasonality, especially during the spring and summer months). CONCLUSIONS: We developed and validated a differentially private federated model by using distributed multi-institutional psychiatric data with standardized pipelines in a real-world environment. The federated model performed better than models using local data only.</p

Incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer

Background: Subsyndromal delirium, a condition in which patients exhibit some, but not all, of the symptoms of delirium, can negatively affect the outcomes of patients with cancer. However, the incidence of subsyndromal delirium in patients with gastric cancer is unknown. Here, we investigated the incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer. Methods: We recruited consecutive patients with gastric cancer who were scheduled for curative resection at a tertiary hospital. Patients&apos; subsyndromal delirium symptoms were serially assessed preoperatively and 1, 2, 3, and 7 days postoperatively using the Delirium Rating Scale-Revised-98 (DRS-R-98). A DRS-R-98 score of 8-14 at any postoperative assessment was considered to indicate subsyndromal delirium. Sociodemographic and pre-/intraoperative clinical data were also assessed. Logistic regression analyses were used to determine the associated risk factors. Results: Data were analysed from 163 out of 217 eligible patients. Postoperative delirium occurred in one patient (0.6%) and subsyndromal delirium occurred in 19 patients (11.7%). Age &gt;= 70 years (odds ratio, [OR] 3.85; 95% confidence interval [0], 136-10.92; p = 0.011) and education level &lt;= 9 years (OR, 3.98; 95% CI, 139-11.41; p= 0.010) were independent risk factors of subsyndromal delirium after adjusting for preoperative cognitive function. Other pre-/intra-operative variables including anxiety/depression, poor sleep quality, and anaesthesia duration were not associated with subsyndromal delirium. Conclusions: In contrast to the low incidence of delirium among patients undergoing curative resection of gastric cancer, a substantial proportion of such patients experienced subsyndromal delirium. Considering the prognostic implications, more careful detection and management of subsyndromal delirium may be warranted in patients with gastric cance

Stenting of the Left Main Coronary Artery in a Patient With Takayasu's Arteritis

Management of Takayasu's arteritis of the left main coronary artery (LMCA) is difficult because of the possibility of restenosis. Clinically significant stenotic lesions must be considered anatomical correlation. Many studies have reported that the management of stenotic lesions of the LMCA with endoluminal stenting and balloon angioplasty and de-novo stenting is safe and effective for patients with Takayasu's arteritis. We report the case of a patient with Takayasu's arteritis of the LMCA. The patient had undergone two consecutive percutaneous coronary interventions because of recurrent restenosis of in-stent lesions, and eventually underwent coronary artery bypass graft (CABG) surgery for myocardial infarction in the same lesion. We suggested treatment with CABG because the pathophysiology of Takayasu's arteritis is different from that of atherosclerotic stenosis

Air Pollution Monitoring and Control System for Subway Stations Using Environmental Sensors

The metropolitan city of Seoul uses more energy than any other area in South Korea due to its high population density. It also has high emissions of air pollutants. Since an individual usually spends most of his/her working hours indoors, the ambient air quality refers to indoor air quality. In particular, PM10 concentration in the underground areas should be monitored to preserve the health of commuters in the subway system. Seoul Metro and Seoul Metropolitan Rapid Transit Corporation measure several air pollutants regularly. In this study, the accuracy of an instrument for PM measurement using the light scattering method was improved with the help of a linear regression analysis technique to continuously measure the PM10 concentrations in subway stations. In addition, an air quality monitoring system based on environmental sensors was implemented to display and record the data of PM10, CO2, temperature, and humidity. Through experimental studies, we found that ventilation fans could improve air quality and decrease PM10 concentrations in the tunnels effectively by increasing the air flow rate

A portable high-intensity focused ultrasound system for the pancreas with 3D electronic steering: a preclinical study in a swine model

Purpose The aim of this animal study was to evaluate the safety and feasibility of a portable, ultrasonography-guided, high-intensity focused ultrasound (USg-HIFU) system to treat the pancreas. Methods Eight swine were included. Using a portable HIFU device (ALPIUS 900, Alpinion Medical Systems), ablations were performed on the pancreas in vivo. Different acoustic intensities were applied (1.7 kW/cm2 or 1.5 kW/cm2, n=2 [group A for a pilot study]; 1.5 kW/ cm2, n=3 [group B]; and 1.2 kW/cm2, n=3 [group C]). Magnetic resonance imaging (MRI) was performed immediately (group A) or 7 days (groups B and C) after HIFU treatment. In groups B and C, serum amylase and lipase levels were measured on days 0 and 7, and performance status was observed every day. Necropsy was performed on days 0 (group A) or 7 (groups B and C) to assess the presence of unintended injuries and to obtain pancreatic and peripancreatic tissue for histological analysis. Results Ablation was noted in the pancreas in all swine on MRI, and all pathologic specimens showed coagulation necrosis in the treated area. The mean ablation areas on MRI were 85.3±38.1 mm2, 90.7±21.2 mm2, and 54.4±30.6 mm2 in groups A, B, and C, respectively (P>0.05). No animals showed evidence of complications, except for one case of a pseudocyst in group B. Conclusion This study showed that pancreas ablation using a portable USg-HIFU system may be safe and feasible, and that coagulation necrosis of the pancreas was successfully achieved with a range of acoustic intensities

The effect of sex and physical frailty on incident disability after 2 years among community-dwelling older adults: KFACS study

Background : This study investigated the impact of physical frailty on the development of disabilities in mobility, activities of daily living (ADL), and instrumental activities of daily living (IADL) according to sex among community-dwelling Korean older adults. Methods : We used data of 2,905 older adults aged 70-84 years from the Korean Frailty and Aging Cohort Study (KFACS) at baseline (2016-2017) and Wave 2 (2018-2019). Fried’s physical frailty phenotype was used to identify frailty. Results : After adjustment, frailty showed a higher impact for women than men on developing mobility disability (odds ratio [OR]=14.00, 95% confidence interval [CI]=4.8–40.78 vs. OR=9.89, 95% CI=4.28–22.86) and IADL disability after two years (OR=7.22, 95% CI=2.67–19.56 vs. OR=3.19, 95% CI=1.17–8.70). Pre-frailty led to mobility disability for women and men (OR=2.77, 95% CI=1.93–3.98 vs. OR=2.49, 95% CI=1.66–3.72, respectively), and IADL disability only for women (OR=3.01, 95% CI=1.28–7.09). Among the IADL components, both men and women who were prefrail or frail showed increased disability in ‘using transportation’. Among men, pre-frailty was significantly associated with disability in “going out” and “shopping”. In women, frailty was significantly associated with disability in “doing laundry,” “performing household chores,” “shopping,” and “managing money”. Conclusions : Physical frailty increased disability over 2 years for women more than men. Physical frailty increased disability in outdoor activity-related IADL components in men and household work-related IADL components in women. This study highlights the need for gender-specific policies and preventative programs for frailty, particularly restorative interventions that focus on women who are physically frail.This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C3153), and the Research Program funded by the National Institute of Health, Korea Disease Control and Prevention Agency (2021-ER060500). The funding bodies had no role in the study design the collection, analysis and interpretation of the data; the writing of the report; or the decision to submit this article for publication

Endoscopic Pancreatic Sphincterotomy: Indications and Complications

Background/Aims: Although a few recent studies have reported the effectiveness of endoscopic pancreatic sphincterotomy (EPST), none has compared physicians' skills and complications resulting from the procedure. Thus, we examined the indications, complications, and safety of EPST performed by a single physician at a single center. Methods: Among 2,313 patients who underwent endoscopic retrograde cholangiopancreatography between January 1996 and March 2008, 46 patients who underwent EPST were included in this retrospective study. We examined the indications, complications, safety, and effectiveness of EPST, as well as the need for a pancreatic drainage procedure and the concomitant application of EPST and endoscopic sphincterotomy (EST). Results: Diagnostic indications for EPST were chronic pancreatitis (26 cases), pancreatic divisum (4 cases), and pancreatic cancer (8 cases). Therapeutic indications for EPST were removal of a pancreaticolith (10 cases), stent insertion for pancreatic duct stenosis (9 cases), nasopancreatic drainage (7 cases), and treatment of sphincter of Oddi dysfunction (1 case). The success rate of EPST was 95.7% (44/46). Acute complications of EPST included five cases (10.9%) of pancreatitis and one of cholangitis (2.2%). EPST with EST did not reduce biliary complications. Endoscopic pancreatic drainage procedures following EPST did not reduce pancreatic complications. Conclusions: EPST showed a low incidence of complications and a high rate of treatment success; thus, EPST is a relatively safe procedure that can be used to treat pancreatic diseases. Pancreatic drainage procedures and additional EST following EPST did not reduce the incidence of procedure-related complications

Proton Magnetic Resonance Spectroscopic Changes of the Primary Motor Cortex and Supplementary Motor Area in Hemiparetic Patients with Corticospinal Tract Injury due to Deep Intracerebral Hematoma

This study was conducted to investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and sup-plementary motor areas (SMA) of 9 hemiparetic patients with documentable hemi-paresis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of inter-est(VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH). 1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were com-pared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were sig-nificantly lower than those of normal volunteers. These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway